The proposed research concerns the synthesis of several classes of compounds that have been shown to possess very important anticancer activity. The development of synthetic pathways for preparing these compounds is vitally important in health-related studies of these materials. The proposed syntheses will provide new sources that will be independent of the limited natural supplies of these compounds. Therefore, the greater availability of these compounds will permit further detailed biomedical investigations of their applications as drugs for treating human cancers. A number of synthetic analogs will also be prepared and submitted for biological testing. This proposal specifically discusses new methods for the synthesis of four classes of anticancer agents: sparsomycin and its analogs, quadrone, germacranolides, and bufadienolides. The proposed pathways involve the use of novel chemical intermediates that promise to be of general use in synthetic organic chemistry. Some types of structures that may be constructed using the new methods are dithioacetal S-oxides, cyclopentenes, acrylates, alpha-methylene lactones, and alpha-pyrones. These methods have all been developed in our preliminary investigations and will be directly applicable to the compounds listed above. A collaborative arrangement has been established between our group and the group of Professor H. C. J. Ottenheijm of the University of Nijmegen in The Netherlands. In our earlier studies, we have already developed successful routes to sparsomycin. The future work in this area will involve optimizing our pathways, determining the presently unknown configuration of the chiral sulfur atom of sparsomycin by a combination of chemical and physical methods, and synthesizing several analogs on a joint basis.